Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
BMC Cancer. 2023 Jun 6;23(1):513. doi: 10.1186/s12885-023-11009-8.
Cancer cachexia, occurring in ~ 80% pancreatic cancer (PC) patients overall, is a paraneoplastic syndrome mediated by cancer-induced systemic inflammation and characterized by weight loss and skeletal muscle wasting. Identifying clinically relevant PC-derived pro-inflammatory factors with cachexigenic potential may provide novel insights and therapeutic strategies.
Pro-inflammatory factors with cachexigenic potential in PC were identified by bioinformatic analysis. The abilities of selected candidate factors in inducing skeletal muscle atrophy were investigated. Expression levels of candidate factors in tumors and sera was compared between PC patients with and without cachexia. Associations between serum levels of the candidates and weight loss were assessed in PC patients.
S100A8, S100A9, and S100A8/A9 were identified and shown to induce C2C12 myotube atrophy. Tumors of PC patients with cachexia had markedly elevated expression of S100A8 (P = 0.003) and S100A9 (P < 0.001). PC patients with cachexia had significantly higher serum levels of S100A8, S100A9 and S100A8/A9. Serum levels of these factors positively correlated with percentage of weight loss [correlation coefficient: S100A8: 0.33 (P < 0.001); S100A9: 0.30 (P < 0.001); S100A8/A9: 0.24 (P = 0.004)] and independently predicted the occurrence of cachexia [adjusted odds ratio (95% confidence interval) per 1ng/ml increase: S100A8 1.11 (1.02-1.21), P = 0.014; S100A9 1.10 (1.04-1.16), P = 0.001; per 1 µg/ml increase: S100A8/A9 1.04 (1.01-1.06), P = 0.009].
Atrophic effects of S100A8, S100A9, and S100A8/A9 indicated them as potential pathogenic factors of PC-induced cachexia. In addition, the correlation with the degree of weight loss and prediction of cachexia in PC patients implicated their potential utility in the diagnosis of PC-induced cachexia.
癌症恶病质发生于约 80%的胰腺癌（PC）患者，是一种癌性诱导的全身炎症介导的副瘤综合征，其特征为体重减轻和骨骼肌消耗。确定具有致恶病质潜能的临床相关 PC 来源的促炎因子可能提供新的见解和治疗策略。
通过生物信息学分析鉴定具有致恶病质潜能的促炎因子。研究了选定候选因子诱导骨骼肌萎缩的能力。比较了恶病质和非恶病质 PC 患者肿瘤和血清中候选因子的表达水平。评估了 PC 患者候选因子血清水平与体重减轻的相关性。
鉴定出 S100A8、S100A9 和 S100A8/A9，并证明它们可诱导 C2C12 肌管萎缩。恶病质 PC 患者的肿瘤中 S100A8（P=0.003）和 S100A9（P<0.001）表达显著升高。恶病质 PC 患者的血清 S100A8、S100A9 和 S100A8/A9 水平显著升高。这些因子的血清水平与体重减轻百分比呈正相关[相关系数：S100A8：0.33（P<0.001）；S100A9：0.30（P<0.001）；S100A8/A9：0.24（P=0.004）]，并独立预测恶病质的发生[每增加 1ng/ml，S100A8 为 1.11（1.02-1.21），P=0.014；S100A9 为 1.10（1.04-1.16），P=0.001；每增加 1μg/ml，S100A8/A9 为 1.04（1.01-1.06），P=0.009]。
S100A8、S100A9 和 S100A8/A9 的萎缩作用表明它们是 PC 诱导恶病质的潜在致病因素。此外，与体重减轻程度的相关性以及对 PC 患者恶病质的预测表明它们在诊断 PC 诱导的恶病质方面具有潜在的应用价值。
